Showing papers in "Current Protein & Peptide Science in 2022"

Calprotectin: the link between acute lung injury and gastrointestinal injury in Covid-19: Ban or boon.

Abstract: The pathogenesis of SARS-CoV-2 infection is related to the direct cytopathic effect and associated hyper-inflammatory due to exaggerated immune response. Different experimental and clinical studies revealed that other biomarkers could be used to determine the Covid-19 severity, such as D-dimer, procalcitonin, C-reaction protein (CRP), IL-6, and ferritin. Calprotectin (CP) is associated with intestinal inflammation, intestinal injury, and different respiratory diseases such as cystic fibrosis. Thus, CP might be a possible biomarker linking intestinal injury and acute lung injury (ALI) in Covid-19. Therefore, this study aimed to find a potential role of CP regarding GITI and ALI in Covid-19. CP is a complex protein consisting of S100A8 and S100A9, belongs to the Ca+2-binding proteins S100 family abundant in the cytosol of neutrophils and expressed on the monocyte membranes, macrophages, and intestinal epithelial cells. CP is a proinflammatory protein that acts through activation of the receptor for the advanced glycation end product (RAGE) and toll-like receptor 4 (TLR4). CP is a biomarker of neutrophil activation and is released following the turnover of neutrophils. CP could be controversial; it increases airway inflammation or protects lung and airway epithelium from an exaggerated immune response. Therefore, a high level of CP in different respiratory disorders might be protective and compensate against abnormal immune responses. CP level is high in Covid-19 and correlated with Covid-19 severity and oxygen demand due to activation release of proinflammatory cytokines and inflammatory signaling pathways. Therefore, CP level is elevated in both ALI and intestinal inflammation so that it could be a potential biomarker link the respiratory and intestinal injury in Covid-19.

Covid-19 and L-arginine supplementations: Yet to find the missed key.

Abstract: Current coronavirus disease (Covid-19) is regarded as a primary respiratory and vascular disease leading to acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and endothelial dysfunction (ED) in severe cases. The causative virus of Covid-19 is SARS-CoV-2, which binds angiotensin-converting enzyme 2 (ACE2) for its entry. It has been shown that ED is linked to various Covid-19 complications since endothelial cells are regarded as the chief barrier against SARS-CoV-2 invasion. SARS-CoV-2-indued ED leads to endotheliitis and thrombosis due to endothelial nitric oxide (NO) inhibition with subsequent vasoconstriction and tissue hypoxia. Loss of vasodilator NO and anti-thrombin factor from endothelial SARS-CoV-2 infection contribute to the progression of vascular dysfunction and coagulopathy. Therefore, NO restoration improves pulmonary function and hinders viral replication during respiratory viral infections, including Covid-19. L-arginine is a semiessential amino acid that has antiviral and immunomodulatory effects as well as it improves the biosynthesis of NO in endothelial cells. L-arginine may reduce risk of ALI through inhibition generation of peroxynitrite and suppression release of proinflammatory cytokines from alveolar macrophages. Of interest, restoration of NO by L-arginine may attenuate SARS-CoV-2 infection through different mechanisms, including reduction binding of SARS-CoV-2 to ACE2, inhibition of transmembrane protease serine type 2 (TMPRSS2) a critical for activation of SARS-CoV-2 spike protein and cellular entry, inhibition proliferation and replication of SARS-CoV-2, and prevention of SARS-CoV-2-induced coagulopathy. In conclusion, through antiviral and immunomodulatory effects, L-arginine and released NO have mutual and interrelated actions against SARS-CoV-2 infection.

Irisin, a mediator of muscle crosstalk with other organs: from metabolism regulation to protective and regenerative effects.

Abstract: Physical exercise is a therapeutic strategy for some systemic and non-systemic complications. Various processes or factors like myokines are involved in an exercise course. Irisin is produced in skeletal muscle during exercise, and its effects resemble many exercise effects. Besides the systemic effects of muscle-derived irisin, this peptide is produced in different tissues. Numerous studies have investigated the underlying molecular mechanisms of irisin effects. Despite some controversies, most studies have demonstrated the improvement of metabolic-related complications and immunomodulatory or regenerative mechanisms in correlation with the circulating level of this peptide or after in vivo/in vitro treatments that have introduced it as a peptide with therapeutic value. This review describes the similarities and differences of the effects in various tissues and their correlation with the most prevalent tissue-related complication to present a view for the mechanism(s) of function, efficacy, and safety of this peptide in each tissue as an exercise effector and endocrine peptide.

Review of post-translational modification of human serum albumin.

Abstract: Post-translational modifications (PTMs) may affect functions of human serum albumin. Here we review reports of novel PTMs of human serum albumin. One hundred twenty-three recently reported novel O-phosphorylation, glycation, methylation, carbonylation, and acetylation of albumin are reviewed. Potential impact of these PTMs on albumin functions is discussed. Knowledge of these PTMs of albumin is of importance for use of albumin in medical applications, e.g., in transfusion, drug formulations and remedies.

Encapsulation of Anabolic Peptide in Lipid Nano Vesicles for Osteoporosis.

Abstract: BACKGROUND Screening of critical variables, including formulation and process variables, in the development of various dosage forms facilitates the identification of the most influencing parameters, which modulate the responses, thereby helping in building the strong quality target product profile. OBJECTIVE The objective of the present work was to screen out the most influential and critical variables for the development of an anabolic peptide encapsulated lipid nanovesicles (PTH-LNVs). METHODS PTH-LNVs were prepared by the ethanol injection method. Taguchi standard orthogonal array L8 design was employed to assess the effect of formulation and processing variables on different response variables. Independent variables considered were drug concentration, lipid concentration, cholesterol concentration, stirring rate, and rate of injection, whereas dependent variables studied were particle size, PDI, zeta potential, % entrapment efficiency, and % drug loading. Particle size, PDI, and zeta potential were evaluated by a zeta sizer. Drug loading efficiency and % entrapment efficiency were determined by HPLC analysis. RESULTS The ethanol injection method was employed to formulate PTH-LNVs using Taguchi standard orthogonal array L8 design. From the half-normal plot and Pareto ranking analysis, it was found that drug, lipid, and cholesterol concentration have a significant effect on responses to formulation and are hence considered critical variables during the formulation development. CONCLUSION The presented work demonstrates the feasibility of Taguchi orthogonal array design in the screening of potential independent factors in the development of peptide encapsulated nanoformulations.

The role of NF-κB in myocardial ischemia/reperfusion injury.

Abstract: Acute myocardial infarction (AMI ) is a threat to human life and physical health all over the world . Timely reperfusion is very important to limit infarct size and protect ischemic myocardium . Unfortunately, it also caused more severer myocardial damage, which is called "myocardial ischemia/reperfusion injury (MIRI )''. There is no effective clinical treatment for it . Over the past two decades, biological studies of NF-κB have improved the understanding of MIRI. Nuclear Factor-κB (NF-κB ) is a major transcription factor associated with cardiovascular health and disease. It is involved in the release of pro-inflammatory factors and apoptosis of cardiomyocytes. Recent studies have shown that inhibition of NF-κB plays a protective role in acute hypoxia and reperfusion injury . Here we review the molecular regulation of NF-κB in MIRI , better understanding of NF-κB signaling mechanisms related to inflammation and crosstalk with endogenous small molecules . We hope this review will aid in improving therapeutic approaches to clinical diagnosing . This review provides evidence for the role of NF-κB in MIRI and supports its use as a therapeutic target .

Implications of CRISPR-Cas9 in developing Next Generation Biofuel: A Minireview.

Abstract: The major drawbacks of biofuel production at the commercial level are its low yield, non-availability of feedstock, feedback inhibition, presence of inhibitory pathways in various organisms, and biofuel intolerance of organisms. The present review focuses on the implications of the CRISPR-Cas9 mediated gene editing tool to alter the genome of bacteria, algae, fungi, and higher plants for efficient biofuel production. Gene knockout and gene cassette insertions employing CRISPR-Cas9 in Saccharomyces cerevisiae and Kluyveromyces marxianus have resulted in enhanced production of bioethanol and 2-Phenyl ethanol in these organisms, respectively. Genomes of several bacterial strains were also modified to enhance ethanol and butanol production in them. CRISPR-Cas9 modification of microalgae has demonstrated improved total lipid content, a prerequisite for biofuel production. All over, CRISPR-Cas9 has emerged as a tool of choice for engineering the genome and metabolic pathways of organisms for producing industrial biofuel. In plant-based biofuel production, the biosynthetic pathways of lignin interfere with the satisfactory release of fermentable sugars thus hampering efficient biofuel production. CRISPR-Cas9 has shown a promising role in reducing lignin content in various plants including barley, switchgrass, and rice straw.

Deciphering the role of S-adenosyl homocysteine nucleosidase in quorum sensing mediated biofilm formation.

Abstract: S-adenosylhomocysteine nucleosidase (MTAN) is a protein that plays a crucial role in several pathways of bacteria that are essential for its survival and pathogenesis. In addition to the role of MTAN in methyl-transfer reactions, methionine biosynthesis, and polyamine synthesis, MTAN is also involved in bacterial quorum sensing (QS). In QS, chemical signaling autoinducer (AI) secreted by bacteria assists cell to cell communication and is regulated in a cell density-dependent manner. They play a significant role in the formation of bacterial biofilm. MTAN plays a major role in the synthesis of these autoinducers. Signaling molecules secreted by bacteria i.e. AI-1 is recognized as acylated homoserine lactones (AHL) that function as signaling molecules within bacteria. QS enables bacteria to establish physical interactions leading to biofilm formation. The formation of biofilm is a primary reason for the development of multidrug-resistant properties in pathogenic bacteria like Enterococcus faecalis (E. faecalis). In this regard, inhibition of E. faecalis MTAN (EfMTAN) will block the QS and alter the bacterial biofilm formation. In addition to this, it will also block methionine biosynthesis and many other critical metabolic processes. It should also be noted that inhibition of EfMTAN will not have any effect on human beings as this enzyme is not present in humans. This review provides a comprehensive overview of the structural-functional relationship of MTAN. We have also highlighted the current status, enigmas that warrant further studies, and the prospects for identifying potential inhibitors of EfMTAN for the treatment of E. faecalis infections. In addition to this, we have also reported structural studies of EfMTAN using homology modeling and highlighted the putative binding sites of the protein.

SARS-CoV-2 infection and C1-esterase inhibitor: Camouflage pattern and new perspective.

Abstract: In Covid-19, the pathological effect of SARS-CoV-2 infection is arbitrated through direct viral toxicity, unusual immune response, endothelial dysfunction, deregulated renin-angiotensin system [RAS], and thrombo-inflammation leading to acute lung injury [ALI], with a succession of acute respiratory distress syndrome [ARDS] in critical conditions. C1 esterase inhibitor [C1INH] is a protease inhibitor that inhibits the spontaneous activation of complement and contact systems and kinin pathway, clotting, and fibrinolytic systems. So, targeting of complement system through activation of C1INH might be a novel therapeutic modality in the treatment of Covid-19. Therefore, this study aims to illustrate the potential nexus between C1INH and the pathophysiology of SARS-CoV-2 infection. C1INH is highly dysregulated in Covid-19 due to inflammatory and coagulation disorders. C1INH is up-regulated in Covid-19 and sepsis as an acute phase response, but this increase is insufficient to block the activated complement system. In addition, the C1INH serum level predicts the development of ARDS in Covid-19 patients, as its up-regulation is associated with the development of cytokine storm. In Covid-19, C1INH might be inhibited or dysregulated by SARS-CoV-2, leading to propagation of complement system activation with subsequent uncontrolled immunological stimulation due to activation of bradykinin and FXII with sequential activation of coagulation cascades and polymerization of fibrin. Thus, suppression of C1INH by SARS-CoV-2 infection leads to thrombosis and excessive inflammation due to uncontrolled activation of complements and contact systems.

Biological functions and applications of antimicrobial peptides.

Abstract: Despite the antimicrobial resistance which has been ascribed to misuse of broad-spectrum antibiotics, the antibiotics could indiscriminately kill pathogenic and beneficial microorganism. These events disrupt the delicate microbial in both humans and animals, which may lead to secondary infection and other negative effects in clinical practice. Antimicrobial peptides (AMPs) are one of the functional natural biopolymers found in plants and animals. Due to their outstanding antimicrobial activity and absence of microbial resistance, the AMPs have attracted enormous research attention. Here, we analyze the antibacterial, antifungal, antiviral, antiparasitic and antitumor properties of the AMPs. We also describe the progress made in research on AMPs. In addition, we highlight recommendations and potential future research strategies for its progress and challenges in practical applications.

Taming the devil: Antimicrobial peptides for safer TB therapeutics.

Abstract: Tuberculosis (TB) is a highly contagious infection with extensive mortality and morbidity. The rise of TB-superbugs (drug-resistant strains) with the increase of their resistance against conventional antibiotics have prompted the further search of new anti-mycobacterial agents. It is difficult to breach the barriers around TB bacteria including mycolic cell wall, granuloma, biofilm and mucus, by conventional antibiotics in a short span of time. Hence, there is an essential need for molecules with an unconventional mode of action and structure that can efficiently break the barriers around mycobacterium. Antimicrobial peptides (AMP) are essential components of innate immunity having cationic and amphipathic characteristics. Lines of evidence show that AMPs have good myco-bactericidal and anti-biofilm activity against normal as well as antibiotic resistant TB bacteria. These peptides have shown direct killing of bacteria by membrane lysis and indirect killing by activation of innate immune response in host cells by interacting with the component of the bacterial membrane and intracellular targets through diverse mechanisms. Despite a good anti-mycobacterial activity, some undesirable characteristics are also associated with AMP including hemolysis, cytotoxicity, susceptibility to proteolysis and poor pharmacokinetic profile, and hence only a few clinical studies have been conducted with these biomolecules. The design of new combinatorial therapies including AMPs and particulate drug delivery systems could be new potential alternatives to conventional antibiotics to fight MDR- and XDR-TB. This review outlined the array of AMP roles in TB therapy, possible mechanisms of actions, activities, and current advances in pragmatic strategies to improve challenges accompanying the delivery of AMP for tuberculosis therapeutics.

Structure, Distribution, Regulation, and Function of Splice Variant Isoforms of Nitric Oxide Synthase Family in the Nervous System.

Abstract: Nitric oxide (NO) is a small molecule, produced by nitric oxide synthase (NOS), with various physio-pathological functions in the body. There are three main NOS isoforms, including the endothelial (eNOS), inducible (iNOS), and neuronal NOS (nNOS), that existing in the peripheral organs and nervous systems of humans and rodents. Moreover, NOS includes other identified NOS isoforms, such as retinal Muller glial cells (mNOS), mitochondrial (mtNOS), penile (PnNOS), testis-specific (TnNOS), and invertebrate Drosophila NOS (dNOS) are the lesser-known types. It is proposed that the versatile functions of NOS isoforms depended on various NOS splice variant subtypes and their expression in the neural (e.g., brain, and spinal cord) and non-neuronal tissues (e.g., lung, kidney, liver and GI tract). Therefore, this review summarizes the NOS subtypes, splice variants, targeted splicing expression in the body, and their proposed physio-pathological functions. At last, alternative NOS subtypes and isoforms, which have previously received scant attention, will be addressed in this article.

Exercise and Metabolic Health: The Emerging Roles of Novel Exerkines.

Abstract: Physical inactivity is a major cause of chronic diseases. It shortens the health span by lowering the age of the first chronic disease onset, which leads to decreased quality of life and increased mortality risk. On the other hand, physical exercise is considered a miracle cure in the primary prevention of at least 35 chronic diseases, including obesity, insulin resistance, and type 2 diabetes. However, despite many scientific attempts to unveil the health benefits conferred by regular exercise, the underlying molecular mechanisms driving such benefits are not fully explored. Recent research shows that exercise-induced bioactive molecules, named exerkines, might play a critical role in the regulation of metabolic homeostasis and thus prevent metabolic diseases. Here we summarize the current understanding of the health-promoting effects of exerkines secreted from skeletal muscle, adipose tissue, bone, and liver, including MOTS-c, BDNF, miR-1, 12,13-diHOME, irisin, spexin, osteocalcin, GDF15, and FGF21 on obesity, insulin resistance, and type 2 diabetes. Identifying the systemic health benefits of exerkines may open a new area for the discovery of new pharmacological strategies for the prevention and management of metabolic diseases.

Comparison of laccases and hemeproteins systems in bioremediation of organic pollutants.

Abstract: AIMS Laccases and peroxidases have a great interest for industrial and environmental applications. These enzymes have a broad substrate range and a robust oxidizing ability. Moreover, using mediators or co-oxidants, makes it possible to increase their catalytic activity and extend their substrate scope to more resistant chemical structures. BACKGROUND Fungal laccases and ligninolytic peroxidases, mainly lignin and manganese peroxidases, are the privileged oxidoreductases for bioremediation processes. Nonetheless, an increasing diversity of laccases and peroxidase-type enzymes has been proposed for environmental technologies. OBJECTIVE This article aims to provide an overview of these enzymes and compare their applicability in the degradation of organic pollutants. METHOD Fundamental properties of the proteins are covered and applications towards polycyclic aromatic hydrocarbons (PAHs) and pesticides are specially focused. RESULT Laccases are multicopper oxidases initially studied for applications in the pulp and paper industry but able to oxidize a variety of environmentally concerning compounds. Relying on O2, laccases do not require peroxides nor auxiliary agents, like Mn2+, although suitable redox mediators are needed to attack the more recalcitrant pollutants (e.g., PAHs). True and pseudo-peroxidases use a stronger oxidant (H2O2) and the redox chemistry at the heme site generates high potential species that allow the oxidation of dyes and some pesticides. CONCLUSION Lately, research efforts have been directed to enzyme discovery, testing with micropollutants, and improving biocatalysts' stability by immobilization and protein engineering. Further understanding of the effects of natural media components and solvents on the enzymes might lead to competitive enzymatic treatments of highly toxic media.

Dysregulation of SNHG16(lncRNA)-Hsa-Let-7b-5p(miRNA)-TUBB4A (mRNA) Pathway Fuels Progression of Skin Cutaneous Melanoma

Abstract: Objective: Skin cutaneous melanoma(SKCM) is the most severe, and complex disease of all skin cancers. The molecular mechanisms of this cancer progression are not well understood. Methods: GEPIA online database was used to validate the differentially expressed genes from two GEO datasets. The prognostic value was calculated by the Kaplan-Meier method. RT-qPCR verified the expression of TUBB4A in SKCM cell line, and the immunohistochemistry of TUBB4A in SKCM and normal skin tissues were gained from Human Protein Atlas. Seven target prediction databases predicted potential microRNAs(miRNAs), and upstream long non-coding RNAs(lncRNAs) were predicted by starBase. The co-expressed gene of TUBB4A was obtained using the two online analysis sites UALCAN and starBase. These co-expressed genes were performed by enrichment analysis, and immune infiltration result was obtained by the TIMER2 online database. The receiver operating characteristic(ROC) curve was applied to evaluate the diagnostic value of TUBB4A in the SKCM and normal skin group. A new nomogram about TUBB4A was constructed to forecast the survival rate of SKCM patients at 1, 3, and 5 years. Results: Firstly, we found that DLL3 and TUBB4A were significantly higher expressed in skin cutaneous melanoma than normal skin. Subsequently, by analyzing progress-free interval(PFI), disease-specific survival(DSS), and disease-free survival(DFS), only TUBB4A was the most potent gene for inhibiting shin cutaneous melanoma progression. In gene ontology(GO)/ kyoto encyclopedia of genes and genomes(KEGG) analysis, TUBB4A may play a key role in the progression of skin cutaneous melanoma by regulating mitochondrial function and affecting cellular metabolism, possibly related to the immune infiltration of CD4+Th1 cells and NK cells. The upstream non-coding RNA(ncRNA) acts through the SNHG16-hsa-let-7b-5p-TUBB4A axis. Conclusion: In conclusion, we elucidated the regulatory role of the SNHG16-hsa-let-7b-5p-TUBB4A axis in the progression of skin cutaneous melanoma by modulating mitochondrial function to affect cellular metabolism. TUBB4A may be a promising diagnostic biomarker and therapeutic target for cutaneous skin melanoma.

Research progress of human AP endonuclease 1: structure, catalytic mechanism and inhibitors.

Abstract: The high stability of phosphodiester bonds is considered to be one of the important reasons for the genetic role of nucleic acids, and their cleavage is also the core of many key biochemical processes, including DNA replication / repair, and RNA processing / degradation. As an important part of the base excision repair (BER) pathway, human apurinic / apyrimidinic endonuclease 1 (APE1) is indispensable for the repair of a basic sites and other DNA damage including ionizing radiation, DNA covalently bonding induced by cytotoxic antitumor drugs, etc. To tumor cells, the DNA repair activity of APE1 may lead to the occurrence of radiotherapy and chemotherapy resistance. Obviously, the overexpression of APE1 often poses a serious threat to the effectiveness of tumor treatment, indicating longer time, much larger dose, less effective chemotherapy and poor prognosis. It is of great urgency to design novel APE1 inhibitors. Rational design and modification of inhibitor molecules are closely related to the research progress of both structural biology and catalytic mechanism. In this review, the structure, catalytic mechanism, inhibitors and other important biochemical information of APE1 all are summarized, which will help for the design and modification of drug molecules targeting APE1.

Dynamics of ubiquitination in differentiation and dedifferentiation of pancreatic β-cells: Putative Target for Diabetes.

Abstract: Impairment in the function of insulin-producing pancreatic β-cells is a hallmark of both type 1 and 2 diabetes (T1D/T2D). Despite nearly a century of efforts to combat acute diabetes burden, there is yet no precise treatment regimen existing. Enhancing the endogenous β-cells either by protecting them from apoptosis or dedifferentiation is a classic alternative approach to retain the β-cell pool. Recent reports have acknowledged the protein homeostasis mediated by the ubiquitin-proteasome system as one of the essential components in maintaining the β-cell pool. Degradation of the targeted substrate by the proteasome is majorly regulated by the ubiquitination status of the targeted protein dictated by E3 ligases and deubiquitinase enzymes. Imbalance in the function of these enzymes results in the malfunction of β-cells and in turn, hyperglycemia. Ubiquitination involves the covalent attachment of one or more ubiquitin moieties to the target protein by E3 ubiquitin ligases and deubiquitinases (DUBs) are the enzymes which antagonize the action of E3 ligases. Having knowledge about different E3 ligases and deubiquitinases in the process of differentiation and dedifferentiation of β-cells, probably paves the way for designing novel modulators that enhance either the differentiation or abate the dedifferentiation process. In this review, we will discuss the importance of the balanced ubiquitination process, an understanding of which would facilitate the restraining of β-cells from exhaustion.

Glucagon-Like Peptide-2 in the Control of Gastrointestinal Motility: Physiological Implications.

Abstract: Glucagon-Like Peptide-2 (GLP-2) is a pleiotropic hormone that plays several roles in different organs and tissues, so being involved in many physiological processes. Among these, it regulates gastrointestinal (GI) tract function binding to a specific G-protein coupled receptor (GLP-2R). Of note, GLP-2R is widely expressed in different cells of the GI tract, including excitatory and inhibitory neurons of the enteric nervous system. In the gut, GLP-2 has been reported to play numerous actions, among which the modulation of motility. Nevertheless, most of the GLP-2 effects and its role in physiological processes are still debated. The aim of this minireview is to summarize the data present in the literature on the control of GI motility by GLP-2, the mechanism through which it occurs, and to discuss the physiological implications of such effects. A better understanding of the role of GLP-2 on GI motor responses may be of importance for the development of new therapeutic approaches in GI dysmotility.

Potential Of Angiotensin-(1-7) In Covid-19 Treatment.

Abstract: The new coronavirus currently named SARS-CoV-2 was announced by the World Health Organization as the virus causing the COVID-19 pandemic. The pathogenesis of SARS-CoV-2 initiates upon contact of a structural spike protein with the angiotensin II-converting enzyme receptor, leading to the induction of inflammatory mechanisms and progression to severe disease in some cases. Currently, studies have emerged linking COVID-19 with angiotensin-(1-7), demonstrating the potential of angiotensin-(1-7)/Mas Receptor axis induction to control disease severity due to its anti-inflammatory, vasodilator, antioxidant, antiproliferative, anticoagulant, antiangiogenic and fibrosis inhibitory effects. The renin angiotensin-system peptide Angiotensin-(1-7) shows a high therapeutic potential for COVID-19 mainly because of its ability to counteract the adverse effects caused in various organs due to angiotensin II-converting enzyme blockade. In light of these factors, the use of convalescent plasma conjugated therapy and Ang (1-7) agonists for the treatment of COVID-19 patients could be recommended. The differential expression of ACE2 and the varied response to SARS-CoV-2 are thought to be connected. According to several investigations, ACE2 antibodies and pharmacological inhibitors might be used to prevent viral entry. Given its capacity to eliminate the virus while ensuring lung and cardiovascular protection by regulating the inflammatory response, angiotensin-(1-7) is expected to be a safe choice. However, more clinical evidence is required to clarify the therapeutic usage of this peptide. The aim of this review article is to present an update of scientific data and clinical trials on the therapeutic potential of angiotensin-(1-7) in patients with COVID-19.

Thymosin β4 and actin: binding modes, biological functions and clinical applications.

Abstract: Thymosin β4 (Tβ4) is the β-thymosin (Tβs) with the highest expression level in human cells; it makes up roughly 70-80% of all Tβs in the human body. Combining the mechanism and activity studies of Tβ4 in recent years, we provide an overview of the subtle molecular mechanism, pharmacological action, and clinical applications of Tβ4. As a G-actin isolator, Tβ4 inhibits the polymerization of G-actin by binding to the matching site of G-actin in a 1:1 ratio through conformational and spatial effects. Tβ4 can control the threshold concentration of G-actin in the cytoplasm, influence the balance of depolymerization and polymerization of F-actin (also called Tread Milling of F-actin), and subsequently affect cell's various physiological activities, especially motility, development and differentiation. Based on this, Tβ4 is known to have a wide range of effects, including regulation of inflammation and tumor metastasis, promotion of angiogenesis, wound healing, regeneration of hair follicles, promotion of the development of the nervous system, and improving bone formation and tooth growth. Tβ4 therefore has extensive medicinal applications in many fields, and serves to preserve the kidney, liver, heart, brain, intestine, and other organs, as well as hair loss, skin trauma, cornea repairing, and other conditions. In this review, we focus on the mechanism of action and clinical application of Tβ4 for its main biological functions.

Use Of Crispr In Infection Control.

Abstract: One of the greatest threats of the global world is infectious diseases. The morbidity and fatality of infectious diseases causes 17 million deaths annually. The recent COVID-19 pandemic describes the uncertain potential of these diseases. Understanding the pathogenesis of infectious agents, including bacteria, viruses, fungi, etc. and the evolution of rapid diagnostic techniques and treatments has become a pressing priority to improve infectious disease outcomes worldwide. Clustered regularly interspaced short palindromic repeats (CRISPR) constitutes the adaptive immune system of archaea and bacteria along with CRISPR-associated (Cas) proteins that recognizes and destroys foreign DNA acting as molecular scissors. Since their discovery, CRISPR systems are classified into 6 types and 22 subtypes. The type II, V and VI are used for diagnostic purposes. This potential of the CRISPR-Cas system is being used to create innovative delivery systems, to access interactions between hosts and pathogens, which helps develop new and improved diagnostics and further advance to prevent and treat infectious diseases.

Overexpression of efflux pumps AcrAB and OqxAB contributes to ciprofloxacin resistance in clinical isolates of K. pneumonia.

Abstract: BACKGROUND Infection caused by multidrug-resistant K. pneumoniae is regarded as a severe public health concern worldwide, with most countries reporting an increase in fatality rates over time. Efflux pumps are significant determinants of acquired and/or intrinsic resistance in K. pneumoniae. OBJECTIVES Our aim is to explore efflux-mediated resistance mechanisms in K. pneumoniae by using quantitative real-time PCR in order to evaluate the expression of efflux pump genes (acrA, acrB, oqxA, and oqxB) and pump regulators (marA, soxS, and rarA). METHOD Efflux pump inhibitor CCCP was able to a reduce MIC values of ciprofloxacin by 2 to 64-fold in 43/46 (93%) of MDR-K. pneumoniae isolates. RESULTS Compared to the control strain (untreated one), our results demonstrated that acrA, acrB, oqxA, oqxB, marA, soxS, and rarA were overexpressed in 29 (63%), 24 (52%), 29 (63%), 24 (52%), 17 (37%), 16 (35%), and 16 (35%) of K. pneumoniae isolates, respectively. Additionally, a positive correlation was established between the expressions of acrAB and marA (r = 0.50, r = 0.45, respectively) and oqxAB and rarA (r = 0.462912, r = 0.519354, respectively). CONCLUSION Ciprofloxacin resistance was caused by overexpression of the efflux pump genes acrAB and oqxAB, as well as the transcriptional regulators marA, soxS, and rarA in clinical isolates of K. pneumonia.

Advanced Protein Drugs and Formulations

Abstract: Previously, the application of proteins was uncommon as therapeutically active molecules. Some of the first applications of proteins as drugs have been insulin and vaccines for overcoming a physiological deficiency and the prevention of diseases, respectively. Nowadays, proteins have many applications, not only as drugs but also as drug delivery systems to be administered by different routes. Due to their nature, the behavior of proteins varies while the conditions of the environment are modified. For this reason, it is necessary to study their behavior for predicting the correct manufacturing, storing, or combination with other possible molecules in a formulation or into the body. The application of techniques for predicting the behavior of proteins in different environments has led to associating this type of behavior into the body with the occurrence of diseases, such as celiac disease or Alzheimer's disease. Thus, this work shows an overview of the main types of proteins applied as active therapeutically molecules, proteins-based drug delivery systems, and techniques for predicting their stability into the primary storing container and the body.

A comprehensive comparative review of protein sequence based computational prediction models of lysine succinylation sites.

Abstract: Lysine succinylation is a post-translational modification (PTM) of protein in which a succinyl group (-CO-CH2-CH2-CO2H) is added to a lysine residue of protein that reverses lysine's positive charge to a negative charge and leads to the significant changes in protein structure and function. It occurs on a wide range of proteins and plays an important role in various cellular and biological processes in both eukaryotes and prokaryotes. Beyond experimentally identified succinylation sites, there have been a lot of studies for developing sequence-based prediction using machine learning approaches, because it has the promise of being extremely time-saving, accurate, robust, and cost-effective. Despite of these benefits on computational prediction of lysine succinylation sites for different species, there are a number of issues that need to be addressed in the design and development of succinylation site predictors. In spite the fact that many studies used different statistical and machine learning computational tools, only a few studies have focused on these bioinformatics issues in depth. Therefore, in this comprehensive comparative review, an attempt is made to present the latest advances in the prediction models, datasets, and online resources, as well as the obstacles and limits, to provide an advantageous guideline for developing more suitable and effective succinylation site prediction tools.

Targeting and Modulation of the Natriuretic Peptide System in Covid-19: A single or double-edged effect?

Abstract: Natriuretic peptide system [NPS] is a group of peptide hormones or paracrine factors, including atrial natriuretic peptide [ANP], brain natriuretic peptide [BNP], and natriuretic peptide precursor C [NPC], that are structurally related. The physiological effects of NPS include natriuresis, increased glomerular filtration rate, inhibition release of renin, vasopressin, and aldosterone, sympathetic inhibition, vasodilatations, and prevents cardiac hypertrophy and remodeling. ANP has immunological effects, as it is also produced locally from immune cells; it regulates innate and adaptive immune responses. Metabolism and degradation of ANP are achieved by neutral endopeptidase [NEP], also known as neprilysin. Coronavirus disease 2019 [Covid-19] pandemic may lead to acute lung injury [ALI] and/or respiratory distress syndrome [ARDS]. The underlying causes of inflammatory and immunological disorders in patients with severe Covid-19 are connected to the immune over-stimulation with the subsequent release of a pro-inflammatory cytokines. Covid-19 severity is linked with high ANP serum levels regardless of acute cardiac injury. Inflammatory stimuli appear to be linked with the release of NPs, which anti-inflammatory effects prevent the development of ALI/ARDS in Covid-19. Therefore, neprilysin inhibitors like sacubitril increase endogenous NPs may reduce the risk of ALI in Covid-19 due to the potentiation of endogenous anti-inflammatory effects of NPs. However, sacubitril increases gastrin-releasing peptide, cathepsin G and release of pro-inflammatory cytokines that are inactivated by neprilysin. In conclusion, NPs and neprilysin have cardio-pulmonary protective effects against Covid-19-induced ALI/ARDS. Neprilysin inhibitor sacubitril has dual protective and harmful effects regarding metabolizing vasoactive peptides by neprilysin. These findings require potential reevaluation of the effect of neprilysin inhibitors in the management of Covid-19.

An Overview of Databases and Bioinformatics Tools for Plant Antimicrobial Peptides

Abstract: Antimicrobial Peptides (AMPs) are small, ribosomally synthesized proteins found in nearly all forms of life. In plants, AMPs play a central role in plant defense due to their distinct physicochemical properties. Due to their broad-spectrum antimicrobial activity and rapid killing action, plant AMPs have become important candidates for the development of new drugs to control plant and animal pathogens that are resistant to multiple drugs. Further research is required to explore the potential uses of these natural compounds. Computational strategies have been increasingly used to understand key aspects of antimicrobial peptides. These strategies will help to minimize the time and cost of "wet-lab" experimentation. Researchers have developed various tools and databases to provide updated information on AMPs. However, despite the increased availability of antimicrobial peptide resources in biological databases, finding AMPs from plants can still be a difficult task. The number of plant AMP sequences in current databases is still small and yet often redundant. To facilitate further characterization of plant AMPs, we have summarized information on the location, distribution, and annotations of plant AMPs available in the most relevant databases for AMPs research. We also mapped and categorized the bioinformatics tools available in these databases. We expect that this will allow researchers to advance in the discovery and development of new plant AMPs with potent biological properties. We hope to provide insights to further expand the application of AMPs in the fields of biotechnology, pharmacy, and agriculture.

A Review: Molecular Mechanism of Regulation of ABCA1 Expression.

Abstract: ATP-binding cassette subfamily A member 1 (ABCA1) protein plays an essential role in a variety of events, such as cholesterol and phospholipid efflux, nascent high-density lipoprotein (HDL) biosynthesis, phospholipid translocation. Thus, there has been much research activity aimed at understanding the molecular mechanisms of regulating ABCA1 expression. In this review, we first discuss ABCA1 structure, tissue distribution, cellular localization, and trafficking, as well as its function. Furthermore, current understanding of the molecular mechanisms involved in the regulation of ABCA1 expression is summarized. ABCA1 transcriptional regulation is mediated by a very complicated system, including nuclear receptor systems, factors binding to other sites in the ABCA1 promoter, cytokines, hormones, growth factors, lipid metabolites, enzymes, and other messengers/factors/pathways. In addition, ABCA1 posttranscriptional regulation is mediated by microRNA, long noncoding RNA, RNA-binding proteins, proteases, fatty acids, PDZ proteins, signaling proteins, and other factors. Compared to the transcriptional regulation of ABCA1, which is well established, the post-transcriptional regulation of ABCA1 expression is poorly understood.

Number of detected proteins as the function of the sensitivity of proteomic technology in human liver cells.

Abstract: AIMS The main goal of the Russian part of C-HPP is to detect and functionally annotate missing proteins (PE2-PE4) encoded by human chromosome 18. To achieve this goal it is necessary to use the most sensitive methods of analysis. BACKGROUND However, identifying such proteins in a complex biological mixture using mass spectrometry (MS)-based methods is difficult due to the insufficient sensitivity of proteomic analysis methods. A possible solution to the problem is the pre-fractionation of a complex biological sample at the sample preparation stage. OBJECTIVE The aims of this study are to measure the detection limit of SRM SIS analysis using a standard set of UPS1 proteins and find a way to enhance the sensitivity of the analysis and to detect proteins encoded by the human chromosome 18 in liver tissue samples and compare the data with transcriptomic analysis of the same samples. METHODS Mass spectrometry, data-dependent acquisition, selected reaction monitoring, high-performance liquid chromatography, data-dependent acquisition in combination with pre-fractionation by alkaline reversed-phase chromatography, selected reaction monitoring in combination with pre-fractionation by alkaline reversed-phase chromatography methods were used in this study. RESULTS The results revealed that 100% of UPS1 proteins in a mixture could only be identified at a concentration of at least 10-9 М. The decrease in concentration leads to protein losses associated with technology sensitivity, and no UPS1 protein is detected at a concentration of 10-13 М. Therefore, the two-dimensional fractionation of samples was applied to improve sensitivity. The human liver tissue was examined by selected reaction monitoring and shotgun methods of MS analysis using one-dimensional and two-dimensional fractionation to identify the proteins encoded by human chromosome 18. A total of 134 proteins were identified. The overlap between proteomic and transcriptomic data in human liver tissue was ~50%. CONCLUSION The sample concentration technique is well suited for a standard UPS1 system that is not contaminated with a complex biological sample. However, it is not suitable for use with a complex biological protein mixture. Thus, it is necessary to develop more sophisticated fractionation systems for the detection of all low-copy proteins. This weak convergence is due to the low sensitivity of proteomic technology compared to transcriptomic approaches. Also, total mRNA was used to perform RNA-seq analysis, but not all detected mRNA molecules could be translated into proteins. This introduces additional uncertainty in the data; in the future, we plan to study only translated mRNA molecules-the translatome. Data is available via ProteomeXchange with identifier PXD026997.

Glycation of Immunoglobulin-G from pentose sugar: A cause for structural perturbations.

Abstract: BACKGROUND Glycation of immunoglobulin-G (IgG) molecule with monosaccharides may cause significant structural disability thus resulting in their loss of function. The accumulation of AGEs formed from glycation play an important role in the aliments associated with metabolic diseases. Therefore, excess of sugar in plasma, interferes with the functioning of IgG and may contribute to wide range of diabetes-associated complications. The long-term formation of these heterogeneous AGEs may accumulate and can affect plasma proteins, especially long-lived proteins. In this study, we analyze glycation of immunoglobulin-G (IgG) with 2'-deoxyribose (deoxyribose) instigated modification in IgG structure and AGEs formation. METHODS This study aims to glycate IgG from varying concentrations of a pentose sugar, 2'-deoxy-ribose (deoxyribose). Post glycation of IgG, both the native and its glycated analogue were characterized by various physicochemical methods and techniques. The glycated protein will be assessed for its stability and perturbations by UV-VIS., fluorescence and FT-IR spectroscopic techniques. Moreover, the early glycation product will be done by NBT assay and other biochemical parameters like HMF, carbonyl content and thioflavin-T assays were also performed to see the biochemical changes induced in the glycated IgG macromolecule. RESULTS Glycation of protein macromolecules generates stable early glycation products (Amadori products). Later on, these Amadori products involve in series of chemical reactions to form more stable advanced glycation end products (AGEs).Our experimental study results could validate the modification in IgG structure and AGEs formation. CONCLUSION The formation of IgG-AGEs from glycation of IgG with deoxyribose could exert cellular toxicity and might initiates secondary complications of diabetes. Therefore, this study emphasized on glycation reaction of IgG from deoxyribose and which has not been reported yet.

Gasdermins: Pore forming proteins as a potential therapeutic target.

Abstract: Gasdermins are novel pore forming proteins that comprise Gasdermin A, Gasdermin B, Gasdermin C, Gasdermin D, Gasdermin E, and Pejvakin (DFNB59). Recently, pyroptosis has been redefined as "Gasdermin mediated necrosis", as gasdermins are key regulators of apoptosis, necrosis, and pyroptosis. The discovery of the gasdermin family has broadened the field of pyroptosis studies. Studies have correlated gasdermins with several diseases. This review summarizes the physiological roles and signal transduction of gasdermins. It further highlights the role of gasdermins in pathological conditions like autoimmune disease, kidney diseases, and central nervous system diseases.